[Mechanism of liver injury induced by alcohol extract of salt-processed Psoraleae Fructus based on chemical modification of protein].

Salt-processed Psoraleae Fructus is a commonly used tonic in clinical practice. However, its usage is restricted due to the inherent toxicity. The covalent modification of proteins by reactive metabolites(RMs) plays a role in the hepatotoxicity of salt-processed Psoraleae Fructus. This study delves into the protein covalent modification by RMs generated from psoralen/isopsoralen, the primary toxic components of salt-processed Psoraleae Fructus, by liquid chromatography-mass spectrometry(LC-MS), aiming to elucidate the mechanism underlying the hepatic injury induced by salt-processed Psoraleae Fructus. Biochemical methods were utilized to measure the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), reduced glutathione(GSH), and glutathione S-transferase(GST) in mice. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining. Subsequently, ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS) was employed to identify the primary toxic components of psoralen/isopsoralen and the RMs in salt-processed Psoraleae Fructus. Covalent bonding adducts of the toxic components/RMs with GSH and free amino acids were identified to investigate the effects of the toxic components on modification sites and patterns of amino acids. The modifications of RMs were incorporated into the variable modifications of Proteome Discoverer, and the target proteins of psoralen/isopsoralen were detected by liquid chromatography-quadrupole exactive-mass spectrometry. Lastly, Label-free quantitative proteomics was adopted to screen differential proteins, which were further subjected to KEGG and GO enrichment analyses and confirmed by qPCR. The results indicated that compared with the control group, salt-processed Psoraleae Fructus significantly elevated the ALT, AST, and MDA levels and lowered the SOD, CAT, GSH, and GST levels in a dose-dependent manner, while causing obvious vacuolization and inflammatory cell infiltration in mouse hepatocytes. Furthermore, the livers of mice in the salt-processed Psoraleae Fructus group showed the presence of five RMs of psoralen/isopsoralen, two adducts with GSH, and one adduct with cysteine. In addition, 10 proteins modified by the RMs of psoralen/isopsoralen were identified. A total of 133 differential proteins were detected in the livers of mice in the salt-processed Psoraleae Fructus group, including 92 with up-regulated expression and 41 with down-regulated expression. These differential proteins mainly involved ribosomes, rRNAs, and glutathione, affecting the proteasome pathway. The qPCR results were consistent with the differential proteins. These findings suggest that the RMs of psoralen/isopsoralen can covalently bind to GSH and modify cysteine and lysine residues of liver proteins. This covalent modification of proteins by harmful substances can potentially result in liver damage. Therefore, it can be inferred that the oxidative stress damage induced by salt-processed Psoraleae Fructus may be associated with the abnormality of proteasome and its complex, biosynthesis of ribosomes and their nucleoprotein complex, rRNA binding, and glutathione binding.

Sleep disturbances and intrinsic capacity trajectories among Chinese older adults: The Rugao Longevity and Ageing Study.

Age related decline of intrinsic capacity (IC) is the core of the functional ability and risk factor of adverse outcomes such as disability, hospitalization, and mortality. However, the relationship between sleep disturbance and IC decline are largely unknown. We conducted a longitudinal study and used data of 1514 community elders from the aging arm of the Rugao Longevity and Ageing Study. We found that poor sleep quality is cross-sectional associated with an increased risk of lower IC. In longitudinal analysis, sleep disturbances were inversely associated with composite IC score changes after adjusting for confounders (PSQI>5 vs. PSQI≤5: mean difference [-0.23], P = 0.0005), suggesting that poor sleep quality was associated with a decline in IC during the follow-up period. In conclusion, sleep disturbances were associated with worse IC changes. The results suggest that improving sleep health may help prevent IC decline and hence decreasing the burden of geriatric nursing practice.

Electrochemical aptasensor based on a dual signal amplification strategy of 1-AP-CNHs and ROP for highly sensitive detection of ERα.

Estrogen receptor alpha (ERα) serves as a crucial biomarker for early breast cancer diagnosis. In this study, we proposed an electrochemical aptasensor with nanomaterial carbon nanohorns/gold nanoparticle composites (1-AP-CNHs/AuNPs) as the substrate, and the primary amine groups on the antibody initiated the ring-opening polymerization (ROP) of monomer amino acid-ferrocene (NCA-Fc) on the electrode surface for ultrasensitive detection of ERα. The composite of 1-AP-CNHs/AuNPs not only possessed more active sites, but also increased the specific surface area of the electrode and allowed a large amount of ferrocene polymer long chains to be grafted onto the electrode surface to achieve signal amplification. Under optimal conditions, the detection limit of the method was 11.995 fg mL-1 with a detection range of 100 fg mL-1-100 ng mL-1. In addition, the biotin-streptavidin system was used to further improve the sensitivity of the sensor. Importantly, this approach could be applied for the practical detection of ERα in real samples.

Investigations on the Performance of a Downhole Electric Heater with Different Parameters Used in Oil Shale In Situ Conversion.

In situ conversion is the most potential technology for efficient and clean development of oil shale, and a downhole electric heater is key equipment for clean, efficient, and low-carbon in situ conversion. Three electric heating rods with different diameters are used to explore their influence on heater performances. The simulation results indicate that increasing the diameter of the heating rod helps to increase the minimum and maximum velocity of shell-side air, and the maximum velocity of H110-24 is 16.34 m/s, which is 1.25 and 1.13 times those of H110-16 and H110-20, respectively. In addition, the location of the local high temperature zone coincides with the area with low air flow velocity, and increasing the diameter of the heating rod can effectively reduce the heating rod surface temperature during high-power heating. Moreover, at the same heat flux, the heat transfer coefficients of H110-24 and H110-20 are 44.82-48.49% and 87.52-95.48% higher than those of H110-16, respectively. With the same heating power, the heat transfer coefficients of heaters have the same trend, indicating that the heat transfer coefficient of the heating rod can be effectively improved by increasing the diameter of the heating rod. Finally, the newly defined comprehensive performance is used to evaluate the heaters with different heating parameters. Increasing the heating power can improve the comprehensive performance of the heater, but the most effective way is to increase the diameter of the heating rod. With the same heating power, the new comprehensive performance of H110-24 and H110-20 is 48.38-52.34% and 87.29-95.19% higher than that of H110-16, respectively, and the electric heating rod with the diameter of 20 mm has the best performance.

Heterogeneous Patterns of Endothelial NF-κB p65 and MAPK c-Jun Activation, Adhesion Molecule Expression, and Leukocyte Recruitment in Lung Microvasculature of Mice with Sepsis.

BACKGROUND: Sepsis is an uncontrolled systemic inflammatory response to an infection that can result in acute failure of the function of the lung called acute respiratory distress syndrome. Leukocyte recruitment is an important hallmark of acute lung failure in patients with sepsis. Endothelial cells (EC) participate in this process by facilitating tethering, rolling, adhesion, and transmigration of leukocytes via adhesion molecules on their cell surface. In in vivo studies, endothelial nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 and mitogen-activated protein kinase (MAPK) c-Jun intracellular signal transduction pathways were reported to regulate the expression of adhesion molecules. METHODS: Mice underwent cecal ligation and puncture (CLP) to induce polymicrobial sepsis and were sacrificed at different time points up to 72 h after sepsis onset. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine the kinetics of nuclear localization of p65 and c-Jun in EC, expression and location of adhesion molecules E-selectin and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, the extent and location of leukocyte recruitment were assessed based on Ly6G staining of neutrophils, cluster determinant (CD) 3 staining of T lymphocytes, and CD68 staining of macrophages. RESULTS: In all pulmonary microvascular beds, we identified p65 and c-Jun nuclear accumulation in a subset of endothelial cells within the first 24 h after CLP-sepsis initiation. E-selectin protein was expressed in a subset of microvessels at 4 and 7 h after sepsis initiation, while VCAM-1 was expressed in a scattered pattern in alveolar tissue and microvessels, without discernible changes during sepsis development. CLP-induced sepsis predominantly promoted the accumulation of neutrophils and T lymphocytes 4 and 7 h after disease onset. Neutrophil accumulation occurred in all pulmonary microvascular beds, while T lymphocytes were present in alveolar tissue and postcapillary venules. Taken together, nuclear localization of p65 and c-Jun in EC and neutrophil recruitment could be associated with induced E-selectin expression in the pulmonary microvessels in CLP-septic mice at the early stage of the disease. In alveolar capillaries, on the other hand, activation of these molecular pathways and leukocyte accumulation occurred in the absence of E-selectin or VCAM-1. CONCLUSIONS: Endothelial activation and leukocyte recruitment in sepsis-induced lung injury are regulated by multiple, heterogeneously controlled mechanisms, which vary depending on the type of microvascular bed involved.

Clinical management of children with tic disorder: insights from therapeutic visits in China-a real-world study.

Objective: This retrospective study aims to investigate the treatment of tic disorder (TD) in Dongfang Hospital affiliated with Beijing University of Chinese Medicine, explore its underlying mechanism, and provide valuable insights for future research and clinical management of TD. Methods: The electronic medical records of children with TD, from 2015 to 2021, were extracted from the information system of Dongfang Hospital affiliated with Beijing University of Chinese Medicine. The clinical characteristics of TD, utilization patterns of Chinese herbal medicine and synthetic drugs in prescriptions, as well as their pharmacological effects, were statistically described and categorized. In addition, association rules and network pharmacology were employed to identify core prescriptions (CPs) and elucidate their microscopic molecular mechanisms in treating TD. Results: The age range of the children was from 6 to 11 years, with a higher proportion of male participants than female ones. The average duration of treatment was 6 weeks. Regimen Z for the treatment of TD can be summarized as follows: Chinese herbal medicine [Saposhnikoviae Radix (FangFeng), Puerariae Lobatae Radix (GeGen), Uncariae Ramulus cum Uncis (GouTeng), Acori Tatarinowii Rhizoma (ShiChangPu), Chuanxiong Rhizoma (ChuanXiong)] and vitamins [lysine, inosite, and vitamin B12 oral solution] form the basic treatment, combined with immunomodulators, antibiotics, electrolyte-balancing agents, and antiallergic agents. CPs primarily exerted their effects through the modulation of gene expression (transcription), the immune system, and signal transduction pathways, with interleukin-4 and interleukin-13 pathways being particularly crucial. Among the lysine synthetic drugs used, inosite and vitamin B12 oral solution were the most frequently prescribed. Conclusion: The regimen Z drug treatment holds significant importance in the field, as it exerts its therapeutic effects through a multitude of pathways and intricate interventions. Chinese herbal medicine primarily regulates immune system-related pathways, while synthetic drugs predominantly consist of vitamins.

Realizing the Direct Synthesis of High Silica IWS Zeolite with Improved Hydrothermal Stability.

Direct synthesis of germanosilicate zeolites with low Ge content and improved hydrothermal stability is a great challenge. Herein, we successfully achieve the direct synthesis of IWS zeolite with a Si/Ge ratio higher than 4 for the first time. High silica IWS zeolites can be prepared in a wide range of Si/Ge ratios (4-16) by utilizing bulky 1,3-bis(1-adamantyl)-imidazolium (BAdaI+) as an efficient organic structure-directing agent from the concentrated synthesis gel under fluoride conditions. It is proven by a series of characterizations that Ge atoms preferentially occupy the double-four-ring (D4R) units. Theoretical calculations reveal the preferential interactions of guest organic structure-directing agents (OSDAs) and host IWS zeolites with different Si/Ge ratios. The introduction of more Ge atoms cannot improve the host-guest interaction when the BAdaI+ molecule is accommodated within the nanopores of IWS zeolite compared to other OSDAs. The obtained IWS zeolite shows an extremely high specific surface area (905 m2/g) and pore volume (1.31 cm3/g). Due to the low Ge content, IWS zeolite exhibits outstanding hydrothermal stability and experiences high temperature steam heating with no loss of crystallinity and only a slight loss of microporosity.

Recruitment of neutrophils in glomeruli in early mouse sepsis is associated with E-selectin expression and activation of endothelial NF-κB and MAPK pathways.

Sepsis is a dysregulated systemic inflammatory response to an infection, which can lead to multiple organ dysfunction syndrome that includes the kidney. Leukocyte recruitment is an important process of the host immune defense in response to sepsis. Endothelial cells (EC) actively regulate leukocyte recruitment by expressing adhesion molecules following the activation of dedicated intracellular signal transduction pathways. Previous studies reported that the expression of adhesion molecules was associated with the activation of endothelial NF-κB p65 and MAPK c-Jun pathways in vitro in response to conditions that mimic processes that occur in inflammation. This study aimed to investigate the spatiotemporal patterns of leukocyte recruitment, expression of adhesion molecules, and endothelial nuclear p65 and c-Jun localization in renal microvascular beds of septic mice. Here, we used a cecal ligation and puncture (CLP) sepsis mouse model and RT-qPCR and immunohistochemical staining. We showed that neutrophils, macrophages, and T lymphocytes were all present in the kidney, yet only neutrophils accumulated in a spatiotemporally discernible pattern, mainly in glomeruli at 4 hours after CLP-sepsis initiation. E-selectin, not VCAM-1, was expressed in glomeruli at the same time point. In a subset of mice at 72 hours after CLP-sepsis started, VCAM-1 expression was prominent in glomerular EC, which was not related to changes in mmu-microRNA(miR)-126a-3p levels, a short noncoding microRNA previously shown to inhibit the translation of VCAM-1 mRNA into protein. Nuclear localization of p65 and c-Jun occurred in EC of all microvascular segments at 4 and 7 hours after CLP-sepsis initiation. In summary, sepsis-induced recruitment of neutrophils, E-selectin expression, and NF-κB p65 and MAPK c-Jun pathway activation coincided in glomeruli at the early stage of the disease. In the other microvascular beds, sepsis led to NF-κB p65 and MAPK c-Jun pathway activation with limited expression of E-selectin and no association with VCAM-1 expression or leukocyte recruitment.

Synthetic community derived from grafted watermelon rhizosphere provides protection for ungrafted watermelon against Fusarium oxysporum via microbial synergistic effects.

BACKGROUND: Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community. RESULTS: Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria. CONCLUSIONS: Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture. Video Abstract.

Integrated Metabolomic-Transcriptomic Analyses of Flavonoid Accumulation in Citrus Fruit under Exogenous Melatonin Treatment.

The flavonoids in citrus fruits are crucial physiological regulators and natural bioactive products of high pharmaceutical value. Melatonin is a pleiotropic hormone that can regulate plant morphogenesis and stress resistance and alter the accumulation of flavonoids in these processes. However, the direct effect of melatonin on citrus flavonoids remains unclear. In this study, nontargeted metabolomics and transcriptomics were utilized to reveal how exogenous melatonin affects flavonoid biosynthesis in "Bingtangcheng" citrus fruits. The melatonin treatment at 0.1 mmol L-1 significantly increased the contents of seven polymethoxylated flavones (PMFs) and up-regulated a series of flavonoid pathway genes, including 4CL (4-coumaroyl CoA ligase), FNS (flavone synthase), and FHs (flavonoid hydroxylases). Meanwhile, CHS (chalcone synthase) was down-regulated, causing a decrease in the content of most flavonoid glycosides. Pearson correlation analysis obtained 21 transcription factors co-expressed with differentially accumulated flavonoids, among which the AP2/EREBP members were the most numerous. Additionally, circadian rhythm and photosynthesis pathways were enriched in the DEG (differentially expressed gene) analysis, suggesting that melatonin might also mediate changes in the flavonoid biosynthesis pathway by affecting the fruit's circadian rhythm. These results provide valuable information for further exploration of the molecular mechanisms through which melatonin regulates citrus fruit metabolism.

Experimental Study on Vacuum Distillation Separation Characteristics of Tar Containing Solid Particles: Distributions of Light Components.

The impacts of the composition and properties of tar products on their utilization are of great importance, while the consequences of varying tar separation conditions on distillation fractions remain underexplored. Solid impurities in special tar products (e.g., subsurface in situ pyrolysis-derived tar-like substances) can contribute to the separation as well. In the present study, low-temperature coal tar (LTCT) was used as an analogue to pyrolysis product, mixed with semi-coke and coal dust, representing pyrolytic byproducts and nonpyrolytic substances, respectively. The LTCT mixtures were tested with vacuum distillation at various pressures and temperatures. The results revealed the role of pressure in fraction distribution across temperatures, with higher pressure concentrating fractions at lower temperatures. The impact of solid impurities on distillation primarily stemmed from adsorption. Minimal concentrations of solid impurities carried coal dust/semi-coke into the distillation, but higher levels retained them in the residue. The adsorption of coal dust was quite high at lower temperatures and waned as temperature increased, unlike semi-coke, which had consistent adsorption throughout the distillation. The present study can advance the understanding of vacuum distillation for tar products in the presence of solid impurities, offering a framework for the effective distillation/utilization of coal tar. By probing separation conditions, tar properties, and solid impurity effects, the present research will refine strategies for optimizing coal tar use, crucial for enhancing energy security and sustainable progress in China.

Assessing the Quality of ChatGPT Responses to Dementia Caregivers' Questions: Qualitative Analysis.

Background: Artificial intelligence (AI) such as ChatGPT by OpenAI holds great promise to improve the quality of life of patients with dementia and their caregivers by providing high-quality responses to their questions about typical dementia behaviors. So far, however, evidence on the quality of such ChatGPT responses is limited. A few recent publications have investigated the quality of ChatGPT responses in other health conditions. Our study is the first to assess ChatGPT using real-world questions asked by dementia caregivers themselves. objectives: This pilot study examines the potential of ChatGPT-3.5 to provide high-quality information that may enhance dementia care and patient-caregiver education. Methods: Our interprofessional team used a formal rating scale (scoring range: 0-5; the higher the score, the better the quality) to evaluate ChatGPT responses to real-world questions posed by dementia caregivers. We selected 60 posts by dementia caregivers from Reddit, a popular social media platform. These posts were verified by 3 interdisciplinary dementia clinicians as representing dementia caregivers' desire for information in the areas of memory loss and confusion, aggression, and driving. Word count for posts in the memory loss and confusion category ranged from 71 to 531 (mean 218; median 188), aggression posts ranged from 58 to 602 words (mean 254; median 200), and driving posts ranged from 93 to 550 words (mean 272; median 276). Results: ChatGPT's response quality scores ranged from 3 to 5. Of the 60 responses, 26 (43%) received 5 points, 21 (35%) received 4 points, and 13 (22%) received 3 points, suggesting high quality. ChatGPT obtained consistently high scores in synthesizing information to provide follow-up recommendations (n=58, 96%), with the lowest scores in the area of comprehensiveness (n=38, 63%). Conclusions: ChatGPT provided high-quality responses to complex questions posted by dementia caregivers, but it did have limitations. ChatGPT was unable to anticipate future problems that a human professional might recognize and address in a clinical encounter. At other times, ChatGPT recommended a strategy that the caregiver had already explicitly tried. This pilot study indicates the potential of AI to provide high-quality information to enhance dementia care and patient-caregiver education in tandem with information provided by licensed health care professionals. Evaluating the quality of responses is necessary to ensure that caregivers can make informed decisions. ChatGPT has the potential to transform health care practice by shaping how caregivers receive health information.

Implications of carbon catabolite repression for Aspergillus-based cell factories: A review.

Carbon catabolite repression (CCR) is a global regulatory mechanism that allows organisms to preferentially utilize a preferred carbon source (usually glucose) by suppressing the expression of genes associated with the utilization of nonpreferred carbon sources. Aspergillus is a large genus of filamentous fungi, some species of which have been used as microbial cell factories for the production of organic acids, industrial enzymes, pharmaceuticals, and other fermented products due to their safety, substrate convenience, and well-established post-translational modifications. Many recent studies have verified that CCR-related genetic alterations can boost the yield of various carbohydrate-active enzymes (CAZymes), even under CCR conditions. Based on these findings, we emphasize that appropriate regulation of the CCR pathway, especially the expression of the key transcription factor CreA gene, has great potential for further expanding the application of Aspergillus cell factories to develop strains for industrial CAZymes production. Further, the genetically modified CCR strains (chassis hosts) can also be used for the production of other useful natural products and recombinant proteins, among others. We here review the regulatory mechanisms of CCR in Aspergillus and its direct application in enzyme production, as well as its potential application in organic acid and pharmaceutical production to illustrate the effects of CCR on Aspergillus cell factories.

Variation of the Orientations of Organic Structure-Directing Agents inside the Channels of SCM-14 and SCM-15 Germanosilicates Obtained by Ab Initio Molecular Dynamic Simulations.

We report ab initio molecular dynamic simulations of the organic structure-directing agent (OSDA) in the channels of SCM-14 and SCM-15 germanosilicates for models with different germanium distribution. Since OSDA was free to move inside the channels, independent of its initial orientation after the simulations in all structures the OSDA, protonated 4-pyrrolidinopyridine, is positioned almost perpendicular to the large channels of SCM-14. The structures obtained from the dynamic simulation are more stable by 157 to 331 kJ/mol than the structures obtained by initial geometry optimization. After simulations, the average distance between the N atom of the pyridine moiety of the OSDA and O from Ge-O-Ge is shorter by 0.2 Å than the same distance obtained from initial optimization. The stretching N-H frequencies in the IR spectra of the OSDA and other calculated vibrational frequencies are not characteristic of the orientation of the molecule and cannot be used to detect it.

A clinical study of non-bioartificial liver DPMAES support system in hepatitis B-related acute-on-chronic liver failure.

This study aims to observe the clinical efficacy of the dual plasma molecular adsorption exchange system (DPMAES) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), with a focus on its regulatory effect on cytokine storm. A total of 60 HBV-ACLF patients were enrolled in this study. The observation group, comprising 30 patients, received DPMAES treatment, while the control group underwent PE treatment. We compared the efficacy changes between the two groups post-treatment. A total of 55 HBV-ACLF patients who completed the study were analyzed, Patients treated with DPMAES showed significant improvements in clinical outcomes. After DPMAES treatment, HBV-ACLF patients exhibited notably 90 day survival rate increased by 18% compared to those in the PE group. Moreover, total bilirubin levels decreased markedly, albumin and platelet levels increased compared to the PE group. After DPMAES treatment, the patient showed a significant decrease in inflammatory cytokine IL-6 (t = 5.046, P < 0.001) and a significant decrease in procalcitonin (t = 4.66, P < 0.001). DPMAES was more effective than PE in rapidly reducing TBiL, improving coagulation function and mitigating cytokine storm. It maintained platelet stability more effectively while minimizing albumin consumption to a greater extent, significantly improved 90-day survival.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076117.

A single-center experience of non-bioartificial DFAPP support systems among Chinese patients with hyperlipidemic moderate/severe acute pancreatitis.

To assess the clinical efficacy of Double Filtration Plasmapheresis (DFAPP), a novel blood purification method, in treating hyperlipidemic moderate/severe pancreatitis (HL-M/SAP). A total of 68 HL-M/SAP patients were enrolled in this study. The observation group, comprising 34 patients, received DFAPP treatment, while the control group underwent CVVH + PA treatment. We compared the efficacy changes between the two groups post-treatment. Patients treated with DFAPP showed significant improvements in clinical outcomes. After 72 h of DFAPP treatment, HL-M/SAP patients exhibited notably lower multiple organ failure scores and a reduced mortality rate compared to those in the CVVH + PA group. Triglyceride levels in HL-M/SAP patients treated with DFAPP for 48 h averaged 3.75 ± 1.95, significantly lower than the 9.57 ± 3.84 levels in the CVVH + PA group (P < 0.05). Moreover, CRP levels decreased markedly, IL-17 levels diminished, IL-10 levels increased, and the decline in IL-35 levels was significantly less pronounced compared to the CVVH + PA group. The recurrence rate of pancreatitis was also significantly lower after 6 months. The early implementation of DFAPP in HL-M/SAP patients effectively reduces triglyceride levels, suppresses pro-inflammatory factors, enhances anti-inflammatory factors, and mitigates cytokine storm-induced sepsis damage. Consequently, this leads to a decrease in the incidence of multiple organ failure, improved patient survival rates, and a reduce the recurrence rate of lipogenic pancreatitis.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076066.

A three-path network with multi-scale selective feature fusion, edge-inspiring and edge-guiding for liver tumor segmentation.

Automatic liver tumor segmentation is one of the most important tasks in computer-aided diagnosis and treatment. Deep learning techniques have gained increasing popularity for medical image segmentation in recent years. However, due to the various shapes, sizes, and obscure boundaries of tumors, it is still difficult to automatically extract tumor regions from CT images. Based on the complementarity of edge detection and region segmentation, a three-path structure with multi-scale selective feature fusion (MSFF) module, multi-channel feature fusion (MFF) module, edge-inspiring (EI) module, and edge-guiding (EG) module is proposed in this paper. The MSFF module includes the process of generation, fusion, and selection of multi-scale features, which can adaptively correct the response weights in multiple branches to filter redundant information. The MFF module integrates richer hierarchical features to capture targets at different scales. The EI module aggregates high-level semantic information at different levels to obtain fine edge semantics, which is injected into the EG module for representation learning of segmentation features. Experiments on the LiTs2017 dataset show that our proposed method achieves a Dice index of 85.55% and a Jaccard index of 81.11%, which are higher than what can be obtained by the current state-of-the-art methods. Cross-dataset validation experiments conducted on 3Dircadb and Clinical datasets show the generalization and robustness of the proposed method by achieving dice indices of 80.14% and 81.68%, respectively.

Denticleless E3 ubiquitin protein ligase (DTL) maintains the proliferation and differentiation of epidermis and hair follicles during skin development.

BACKGROUND: A precise balance between the proliferation and differentiation of epidermal progenitors is required to achieve the barrier function during the development of epidermis. During the entire process of skin development, the newly formed basal layer cells divide, differentiate, and migrate outward to the surface of the skin, which is tightly regulated by a series of events related to cell cycle progression. The CRL4DTL complex (Cullin 4 RING ligase, in association with the substrate receptor DTL) has long emerged as a master regulator in various cellular processes, which mediates the degradation of key cell cycle proteins. However, the roles of DTL in regulating epidermal morphogenesis during skin development remain unclear. RESULTS: We showed that DTL deficiency in epidermal progenitor cells leads to defects in epidermal stratification and loss of hair follicles accompanied by reduced epidermal progenitor cells and disturbed cell cycle progression during skin development. Transcriptome analysis revealed that p53 pathway is activated in DTL-depleted epidermal progenitor cells. The apoptosis of epidermal cells showed in DTL deficiency mice is rescued by the absence of p53, but the proliferation and differentiation defects were p53-independent. CONCLUSION: Our findings indicate that DTL plays a vital role in epidermal malformation during skin development.